A new class of antimalarial drugs has worked remarkably well in animal trials. The new compound inhibits the parasites' ability to synthesize protective membranes while sequestered away inside red blood cells. Although it's still too early to tell for sure, the compound could provide just what researchers have been searching for: a potent and inexpensive drug that makes it hard for the parasite to acquire resistance.
The new drug takes aim at the malaria parasite while it resides in red blood cells. Each of these merozoites, as the parasite is called in this stage of its life cycle, produces about 20 progeny. These erupt from the cell, reinvade the bloodstream, and colonize yet more red blood cells. The parasites can eventually colonize and destroy up to 70% of all red blood cells, causing severe anemia, fever, convulsions, coma, and death.
But biochemist Henri Vial of the University of Montpellier II and the Centre National de la Recherche Scientifique in France sensed that the parasite was vulnerable: The merozoites have to package their progeny in protective lipid membranes or they won't survive. Vial reasoned that targeting the mechanism for building these membranes would stop the parasite in its tracks without harming healthy red blood cells, which don't synthesize lipids on their own.
The new drug, dubbed G25, interferes with the parasite's ability to use choline from blood plasma to build the major component of its protective membranes. Vial and colleagues gave G25 to rodents and monkeys infected with Plasmodium falciparum, the most lethal malaria parasite. Low doses of G25 cured the animals quickly and completely, the team reports in the 15 February issue of Science.
The compound "seems to be extremely potent and active against even multidrug-resistant strains of P. falciparum," says David Fidock, a molecular parasitologist at the Albert Einstein College of Medicine in New York City. Plus it is both easy to make and inexpensive--essential qualities for a drug that would be used in sub-Saharan Africa, where 90% of all malaria cases arise, and Southeast Asia, both of which are plagued by multidrug-resistant malaria. One drawback is that the drug must be injected. However, Vial says his team hopes to have an oral candidate for preclinical studies within 2 years.